PENTAZOCINE AND NALOXONE- pentazocine and naloxone hydrochloride tablet
Sun Pharmaceutical Industries, Inc.
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
Pentazocine and Naloxone Tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Pentazocine and Naloxone Tablets, and monitor all patients regularly for the development of these behaviors and conditions [see WARNINGS].
Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS):
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products [see Warnings]. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to
- complete a REMS-compliant education program,
- counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
- emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
- consider other tools to improve patient, household, and community safety.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of Pentazocine and Naloxone Tablets. Monitor for respiratory depression, especially during initiation of Pentazocine and Naloxone Tablets or following a dose increase [see WARNINGS].
Accidental ingestion of even one dose of Pentazocine and Naloxone Tablets, especially by children, can result in a fatal overdose of Pentazocine [see WARNINGS].
Neonatal Opioid Withdrawal Syndrome
Prolonged use of Pentazocine and Naloxone Tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see WARNINGS].
- Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
- Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [ see Warnings and Precautions (5.X), Drug Interactions (7.X)].
- Reserve concomitant prescribing of Pentazocine and Naloxone Tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
- Limit dosages and durations to the minimum required.
- Follow patients for signs and symptoms of respiratory depression and sedation.
Pentazocine and Naloxone Hydrochloride Tablets, USP contain pentazocine hydrochloride, USP, a partial opioid agonist, equivalent to 50 mg base and is a member of the benzazocine series (also known as the benzomorphan series), and naloxone hydrochloride, USP, an opioid antagonist equivalent to 0.5 mg base.
Pentazocine and Naloxone Hydrochloride Tablets, USP are an analgesic for oral administration.
Chemically, pentazocine hydrochloride is (2R*,6R*,11R*)- 1, 2, 3, 4, 5, 6- Hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol hydrochloride, a white, crystalline substance soluble in acidic aqueous solutions, and has the following structural formula:
Chemically, naloxone hydrochloride is 17-Allyl-4,5a-epoxy-3,14-dihydroxy‑ morphinan-6-one hydrochloride. It is a slightly off-white powder, and is soluble in water and dilute acids, and has the following structural formula:
Each tablet, for oral administration, contains pentazocine hydrochloride, USP, equivalent to 50 mg of pentazocine, and naloxone hydrochloride, USP, equivalent to 0.5 mg of naloxone. In addition, each tablet contains the following inactive ingredients: Colloidal Silicon Dioxide, Corn Starch, Dibasic Calcium Phosphate, D&C Yellow #10
Aluminum lake, Magnesium Stearate, Microcrystalline Cellulose, Sodium Lauryl Sulfate.
Mechanism of Action
Pentazocine is a mixed agonist-antagonist at opioid receptors. Pentazocine is a partial agonist at the mu opioid receptor and an agonist at the kappa opioid receptor.
Naloxone is an opioid antagonist.
Pentazocine produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Pentazocine causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Pentazocine causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.
Pentazocine produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions ]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.
Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions ].
Opioids have been shown to have a variety of effects on components of the immune system. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.
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